Analysis of Gastric Cancer Transcriptomic Data by Bioinformatics Tools and Detection of Candidate Diagnostic Biomarker Genes

Main Article Content

Semih Dalkilic

Keywords

Gastric cancer, Gene expression, Bioinformatics, Biomarker

Abstract

Background: Gastric cancer is one of the leading cause of deaths in the world and each year many new cases diagnosed worldwide. Although there has been a decrease in its incidence over the past century, gastric cancer is the second leading cause of cancer-related deaths. Objective: The main objective of this study is identification of candidate biomarker genes to be used in early diagnosis of gastric cancer. Methods: In this study, GSE54129 data set in the Gene Expression Omnibus (GEO) database was used. This data set contains gene expression data of 111 stomach cancer tumor tissues and 21 normal stomach tissues. Bioinformatics analyses performed on raw microarray data (CEL files). All the analyses were performed with Transcriptome Analysis Console 4.0 (TAC) algorithm. Results: According to the results, expression level of many genes during neoplastic transformation in gastric cancer significantly changes when compared to healthy control subjects. The upregulated genes which show high fold changes are SFRP2, EGR1, CHI3L1, COL8A1, NEAT1, INHBA, CXCL8 and MYL9. Some of downregulated genes with higher fold changes are GAST, GIF, GKN2, GKN1, SCGB2A1, and HRASLS2. Conclusion: These genes have a potential for candidate biomarkers that can be used in the diagnosis or detection of molecular subtypes of gastric cancer.

Abstract 936 | PDF Downloads 411

References

1. Petrovchich I, and Ford JM. Genetic predisposition to gastric cancer. Semin Oncol. 2016: 43(5):554-559.
2. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F,. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014: 23(5):700-13. doi: 10.1158/1055-9965.EPI-13-1057.
3. Baretton GB, and Aust DE. Current biomarkers for gastric cancer. Pathologe. 2017: 38(2):93-97.
4. Çaycı HM, Erdoğdu UE, Çantay H, Orman S, Mustafa AKAR, & Demirci H,. Mide kanseri deneyimlerimiz: Tanı ve tedavide geç mi kalıyoruz?. Akademik gastroenteroloji dergisi, 2017: 16(1), 6-11.
5. Alacalı M. Mide kanseri, mide kanseri taramaları ve mide kanserinden korunma. Ankara Medical Journal, 2012: 12(4).
6. Jemal A, Bray F, Center MM, Ferlay J, Ward E, & Forman D. Global cancer statistics. CA: a cancer journal for clinicians, 2011: 61(2), 69-90.
7. Göral V, Yeşilbağdan H, Kaplan A, Şit D, & Çelik M. Mide kanserinde yeni bir tümör markeri olan CA 72-4'ün yeri. Turkiye Klinikleri Journal of Medical Sciences, 2006: 26(1), 3-8.
8. Yüksel BC, Uçar NS, Yıldız Y, Berkem H, Özel H, & Hengirmen S. Mide kanserinde standart D2 diseksiyona karşı D1 diseksiyonun mortalite ve morbidite çalışması. Turkish Journal of Surgery/Ulusal Cerrahi Dergisi, 2009: 25(3).
9. Matsuoka T. and Yashiro M,. "Biomarkers of gastric cancer: current topics and future perspective." World J Gastroenterol . 2018: 24(26): 2818.
10. Necula L, Matei L, et al. "Recent advances in gastric cancer early diagnosis." World J Gastroenterol 2019: 25(17): 2029.
11. Tunca B, Aksoy SA, Mutlu M, & Tekin Ç. Mide Kanserinde Genetik ve Epigenetik Mekanizmaların Rolü. Turkiye Klinikleri Radiation Oncology-Special Topics, 2019: 5(1), 7-14.
12. Li H, Yu B, Li J, Su L, Yan M, Zhang J, Li Cı, Zhu Z, Liu B,. Characterization of differentially expressed genes involved in pathways associated with gastric cancer. PLoS One. 2015: 30;10(4).
13. Shekari N, Baradaran B, Shanehbandi D, Kazemi T,. Circulating MicroRNAs: Valuable Biomarkers for the Diagnosis and Prognosis of Gastric Cancer. Curr Med Chem. 2018: 25(6):698-714.
14. Yi, Zhu., Xiangwei, Sun., Ji, Lin., Teming, Zhang., Xin, Liu., Xian, Shen., Investigating Potential Molecular Mechanisms of Carcinogenesis and Genes as Biomarkers for Prognosis of Gastric Cancer Based on Integrated Bioinformatics Analysis. Pathology & Oncology Research 2019: 25:1125–1133.
15. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009: 4(1):44-57.
16. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009: 37(1):1-13.
17. Baharudin, R., Tieng, F. Y. F., Lee, L. H., & Ab Mutalib, N. SEpigenetics of SFRP1: The Dual Roles in Human Cancers. Cancers. 2020: 12(2)-445.
18. Bovolenta P, Esteve P, Ruiz JM, Cisneros E, Lopez-Rios J. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J. Cell Sci. 2008: 121, 737–746.
19. Atschekzei F, Hennenlotter J, Jänisch S, Großhennig A, Tränkenschuh W, Waalkes S, Peters I, Dörk T, Merseburger AS, Stenzl A, et al. SFRP1 CpG island methylation locus is associated with renal cell cancer susceptibility and disease recurrence. Epigenetics 2012: 7, 447–457.
20. Jin Y, Feng S.J, Qiu S, Shao N, Zheng J.H. LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway. Eur Rev Med Pharmacol Sci. 2017: 21(14), 3176-3184.
21. Xia H, Chen Q, Chen Y, Ge X, Leng W, Tang Q, Ren M, Chen L, Yuan D, Zhang Y, Liu M, Gong Q, Bi F. The lncRNA MALAT1 is a novel biomarker for gastric cancer metastasis. Oncotarget. 2016: 7(35):56209-56218.
22. Huang T, Wang L, Liu D, Li P, Xiong H, Zhuang L, Qiu H. FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1. International journal of oncology. 2017: 50(5), 1501-1512.
23. Dahia, Patricia L. PTEN, a unique tumor suppressor gene. Endocrine-related cancer. 2000; 7.2: 115-129.
24. Manning, Brendan D., and Lewis C. Cantley. "AKT/PKB signaling: navigating downstream." Cell. 2007: 129.7 1261-127